Methanol → Methyl 2-(2-chloro-2',6'-difluoro-4'-hydroxybiphenyl-4-yl)acetate
Reaction equation
B(Br)(Br)Br.[Cl:5][C:6]1[CH:11]=[C:10]([CH2:12][C:13]([OH:15])=[O:14])[CH:9]=[CH:8][C:7]=1[C:16]1[C:21]([F:22])=[CH:20][C:19]([O:23]C)=[CH:18][C:17]=1[F:25].[CH3:26]O>ClCCl>[Cl:5][C:6]1[CH:11]=[C:10]([CH2:12][C:13]([O:15][CH3:26])=[O:14])[CH:9]=[CH:8][C:7]=1[C:16]1[C:21]([F:22])=[CH:20][C:19]([OH:23])=[CH:18][C:17]=1[F:25]Participants
Procedure
Boron tribromide (1.494 mL, 15.80 mmol) was added dropwise to 2-(2-chloro-2′,6′-difluoro-4′-methoxybiphenyl-4-yl)acetic acid (Intermediate 2-5; 822 mg, 2.63 mmol) in dichloromethane (30 mL) at ambient temperature under nitrogen. The resulting solution was stirred at ambient temperature for 90 minutes. The reaction mixture was cautiously added to ice water cooled methanol (50 mL) and the mixture was stirred for a further 20 minutes. The reaction mixture was evaporated to dryness and redissolved in EtOAc (150 mL), and washed sequentially with 2M HCl (50 mL) and saturated brine (50 mL). The organic layer was dried over MgSO4, filtered and evaporated to afford methyl 2-(2-chloro-2′,6′-difluoro-4′-hydroxybiphenyl-4-yl)acetate (822 mg, 100%) as a yellow gum.
Workup
- stirringthe mixture was stirred for a further 20 minutes
- customThe reaction mixture was evaporated to dryness
- dissolutionredissolved in EtOAc (150 mL)
- washwashed sequentially with 2M HCl (50 mL) and saturated brine (50 mL)
- dry with materialThe organic layer was dried over MgSO4
- filtrationfiltered
- customevaporated
Sources & evidence
- ORD record
- ord-aa3013bcf67543ef97e805665623c991
- Source dataset
- uspto-grants-2012_05
- Patent number
- US08188092B2
Reaction notes
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